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Overview

This OpenSAFELY report was rapidly developed to support monitoring the ongoing roll-out of neutralising monoclonal antibodies (nMABs) and antivirals for treatment of COVID-19, based on the population of 23.4m people registered with practices that use TPP SystmOne software. This report will be updated approximately weekly as new data arrives.

The code and data for this report can be found at the OpenSAFELY antibody-and-antiviral-deployment repository. The accompanying manuscript will be available shortly on MedRXiV (link to follow) and submitted for peer review.

Introduction

While vaccines remain the best strategy to prevent COVID-19, recent evidence suggests neutralising monoclonal antibodies (nMABs) or antivirals could potentially benefit certain vulnerable populations before or after exposure to SARS-CoV-2, such as the unvaccinated or recently vaccinated high-risk patients.

With the recent roll-out of nMABs and antivirals, there is an urgent need to for knowledge and understanding around the use of these treatments in patients with COVID-19, such as factors of relevance in determining nMAB and antiviral treatment and the impact of nMAB and antiviral treatment in the community and hospital settings.

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods can be found at the end of the this report.

Results

Overall coverage of COVID-19 treatment

Between 11-Dec-2021 and 23-Feb-2022, a total of 50,730 non-hospitalised patients registered at a TPP practice in England were identified as being eligible for receiving an antiviral or nMABs for treating COVID-19 (Figure 1). While the majority of these patients only belonged to one high risk cohort, 7,690 (15%) eligible patients had records indicating that they fell into multiple high risk cohorts (high risk cohort count range 1 - 6). Out of the 50,730 eligible patients, a total of 6,460 patients received an antiviral or nMABs (Figures 2 and 3);

  • Paxlovid: 110;
  • Sotrovimab: 3,610;
  • Remdesivir: 0;
  • Molnupiravir: 2,680;
  • Casirivimab: 50.
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Figure 1: Cumulative total of patients eligible for receiving an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohort. Patients are included as eligible on the date of their positive SARS-CoV-2 test. Note, eligible patients can appear in more than one high risk group and the overall number (pre 10th February 2022) in each group is likely to be an overestimation due to including patients where their SARS-CoV-2 infection is confirmed by a lateral flow or polymerase chain reaction test.

Figure 1: Cumulative total of patients eligible for receiving an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohort. Patients are included as eligible on the date of their positive SARS-CoV-2 test. Note, eligible patients can appear in more than one high risk group and the overall number (pre 10th February 2022) in each group is likely to be an overestimation due to including patients where their SARS-CoV-2 infection is confirmed by a lateral flow or polymerase chain reaction test.

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Figure 2: Cumulative total of patients who received an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by treatment type

Figure 2: Cumulative total of patients who received an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by treatment type

Coverage of COVID-19 treatment by high risk cohort

Figure 3: Cumulative total of patients who received an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohorts. Note, treated patients can appear in more than one high risk group.

Figure 3: Cumulative total of patients who received an antiviral or nMABs for treating COVID-19 since 11th December 2021, stratified by high risk cohorts. Note, treated patients can appear in more than one high risk group.

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Figure 4: Weekly proportion of eligible patients receiving an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by high risk cohort

Figure 4: Weekly proportion of eligible patients receiving an antiviral or nMAB for treating COVID-19 since 11th December 2021, stratified by high risk cohort

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Table 1: Count and proportion of eligible patients who have received treatment for COVID-19 since 11th December 2021, broken down by high risk cohort and treatment type
Treated
Eligible
All
Paxlovid
Sotrovimab
Remdesivir
Molnupiravir
Casirivimab
High risk cohort Count Count % Count % Count % Count % Count % Count %
All 50730 6420 13 (12-13) 80 1 (1-2) 3600 56 (55-57) <5 – 2680 42 (41-43) 50 1 (1-1)
Immuosupression due to HIV or AIDS (CD4 <350 cells/mm3) 330 190 58 (52-63) <5 – 70 37 (30-44) <5 – 120 63 (56-70) <5 –
Renal disease 3160 800 25 (24-27) <5 – 540 68 (64-71) <5 – 260 32 (29-36) 10 1 (0-2)
Solid organ transplant recipients 3490 860 25 (23-26) <5 – 560 65 (62-68) <5 – 290 34 (31-37) 10 1 (0-2)
Haematological diseases and stem cell transplant recipients 4530 930 21 (19-22) 10 1 (0-2) 520 56 (53-59) <5 – 390 42 (39-45) 10 1 (0-2)
Rare neurological conditions 5680 920 16 (15-17) 20 2 (1-3) 480 52 (49-55) <5 – 420 46 (42-49) 10 1 (0-2)
Immune-mediated inflammatory disorders 20390 3030 15 (14-15) 30 1 (1-1) 1720 57 (55-59) <5 – 1250 41 (40-43) 20 1 (0-1)
Down’s syndrome 1090 150 14 (12-16) <5 – 50 33 (26-41) <5 – 100 67 (59-74) <5 –
Primary immune deficiencies 9940 1190 12 (11-13) 20 2 (1-2) 620 52 (49-55) <5 – 540 45 (43-48) 10 1 (0-1)
Solid cancer 8370 950 11 (11-12) 10 1 (0-2) 550 58 (55-61) <5 – 380 40 (37-43) 10 1 (0-2)
Liver disease 3130 320 10 (9-11) <5 – 170 53 (48-59) <5 – 140 44 (38-49) <5 –
* High risk cohorts are arranged in descending order, according to percentage treated
† All percentages (%) are caluclated with 95% confidence intervals

Key demographic and clinical characteristics of treated patients

Table 2: Count and proportion of eligible patients who have received treatment for COVID-19, broken down by demographic and clinical categories and by treatment type
Treated
Eligible
All
Paxlovid
Sotrovimab
Remdesivir
Molnupiravir
Casirivimab
Group Variable Count Count % Count % Count % Count % Count % Count %
Age band 12-29 5050 550 11 (10-12) 10 2 (1-3) 300 55 (50-59) <5 – 230 42 (38-46) 10 2 (1-3)
Age band 30-39 6470 990 15 (14-16) 10 1 (0-2) 570 58 (54-61) <5 – 390 39 (36-42) 10 1 (0-2)
Age band 40-49 8390 1320 16 (15-17) 20 2 (1-2) 750 57 (54-59) <5 – 530 40 (38-43) 10 1 (0-1)
Age band 50-59 10050 1450 14 (14-15) 40 3 (2-4) 820 57 (54-59) <5 – 580 40 (37-43) 10 1 (0-1)
Age band 60-69 8740 1130 13 (12-14) 20 2 (1-3) 640 57 (54-60) <5 – 460 41 (38-44) 10 1 (0-1)
Age band 70-79 7330 760 10 (10-11) 10 1 (1-2) 410 54 (50-57) <5 – 340 45 (41-48) <5 –
Age band 80+ 4700 270 6 (5-6) <5 – 110 41 (35-47) <5 – 150 56 (50-61) <5 –
Sex Female 28640 3810 13 (13-14) 70 2 (1-2) 2170 57 (55-59) <5 – 1550 41 (39-42) 20 1 (0-1)
Sex Male 22090 2650 12 (12-12) 40 2 (1-2) 1440 54 (52-56) <5 – 1130 43 (41-45) 30 1 (1-2)
Sex Unknown <5 <5 – <5 – <5 – <5 – <5 – <5 –
Ethnicity White 40570 5480 14 (13-14) 100 2 (1-2) 3090 56 (55-58) <5 – 2240 41 (40-42) 40 1 (1-1)
Ethnicity Asian or Asian British 2540 330 13 (12-14) <5 – 210 64 (58-69) <5 – 120 36 (31-42) <5 –
Ethnicity Black or Black British 2030 190 9 (8-11) <5 – 100 53 (46-60) <5 – 80 42 (35-49) <5 –
Ethnicity Mixed 670 80 12 (9-14) <5 – 40 50 (39-61) <5 – 40 50 (39-61) <5 –
Ethnicity Other ethnic groups 830 90 11 (9-13) <5 – 40 44 (34-55) <5 – 50 56 (45-66) <5 –
Ethnicity Unknown 4090 290 7 (6-8) 10 3 (1-6) 130 45 (39-51) <5 – 150 52 (46-57) <5 –
IMD 1 most deprived 10310 920 9 (8-9) 20 2 (1-3) 530 58 (54-61) <5 – 370 40 (37-43) 10 1 (0-2)
IMD 2 10000 1180 12 (11-12) 20 2 (1-2) 650 55 (52-58) <5 – 500 42 (40-45) 10 1 (0-1)
IMD 3 10340 1450 14 (13-15) 20 1 (1-2) 800 55 (53-58) <5 – 610 42 (40-45) 10 1 (0-1)
IMD 4 9720 1350 14 (13-15) 20 1 (1-2) 770 57 (54-60) <5 – 550 41 (38-43) 10 1 (0-1)
IMD 5 least deprived 8970 1380 15 (15-16) 30 2 (1-3) 760 55 (52-58) <5 – 580 42 (39-45) 10 1 (0-1)
IMD Unknown 1400 180 13 (11-15) <5 – 100 56 (48-63) <5 – 80 44 (37-52) <5 –
Rurality Urban - conurbation 13660 1370 10 (10-11) 20 1 (1-2) 770 56 (54-59) <5 – 580 42 (40-45) <5 –
Rurality Urban - city and town 26040 3470 13 (13-14) 70 2 (2-2) 1840 53 (51-55) <5 – 1520 44 (42-45) 30 1 (1-1)
Rurality Rural - town and fringe 5900 850 14 (14-15) 10 1 (0-2) 520 61 (58-64) <5 – 310 36 (33-40) 10 1 (0-2)
Rurality Rural - village and dispersed 3790 590 16 (14-17) 10 2 (1-3) 380 64 (61-68) <5 – 200 34 (30-38) 0 0 (0-0)
Rurality Unknown 1350 180 13 (12-15) <5 – 100 56 (48-63) <5 – 80 44 (37-52) <5 –
Region East Midlands 9050 1060 12 (11-12) 20 2 (1-3) 740 70 (67-73) <5 – 280 26 (24-29) 20 2 (1-3)
Region East of England 12000 2040 17 (16-18) 10 0 (0-1) 1110 54 (52-57) <5 – 890 44 (41-46) 20 1 (1-1)
Region London 3210 420 13 (12-14) 10 2 (1-4) 160 38 (33-43) <5 – 250 60 (55-64) <5 –
Region North East 2730 320 12 (11-13) <5 – 240 75 (70-80) <5 – 80 25 (20-30) <5 –
Region North West 5340 610 11 (11-12) 20 3 (2-5) 300 49 (45-53) <5 – 290 48 (44-52) <5 –
Region South East 3240 430 13 (12-14) 10 2 (1-4) 240 56 (51-61) <5 – 180 42 (37-47) <5 –
Region South West 5880 940 16 (15-17) 30 3 (2-4) 440 47 (44-50) <5 – 460 49 (46-52) <5 –
Region West Midlands 2080 250 12 (11-13) <5 – 200 80 (75-85) <5 – 50 20 (15-25) <5 –
Region Yorkshire and the Humber 7140 400 6 (5-6) 10 2 (1-4) 180 45 (40-50) <5 – 210 52 (48-57) <5 –
Region Unknown 70 10 14 (6-22) <5 – 0 0 (0-0) <5 – <5 – <5 –
Autism Autism 300 40 13 (9-17) <5 – 20 50 (35-65) <5 – 30 75 (62-88) <5 –
Care home Care home 1700 60 4 (3-4) <5 – 10 17 (7-26) <5 – 50 83 (74-93) <5 –
Dementia Dementia 1230 50 4 (3-5) <5 – 10 20 (9-31) <5 – 30 60 (46-74) <5 –
Learning disability Learning disability 1310 170 13 (11-15) 0 0 (0-0) 60 35 (28-42) <5 – 100 59 (51-66) <5 –
Serious mental illness Serious mental illness 700 70 10 (8-12) <5 – 30 43 (31-54) <5 – 30 43 (31-54) <5 –
Housebound Housebound 1830 180 10 (8-11) <5 – 90 50 (43-57) <5 – 80 44 (37-52) <5 –
CEV CEV 26850 4570 17 (17-17) 70 2 (1-2) 2600 57 (55-58) <5 – 1860 41 (39-42) 40 1 (1-1)
Sickle cell disease Sickle cell disease 750 50 7 (5-8) <5 – 20 40 (26-54) <5 – 20 40 (26-54) <5 –
Vaccination status Un-vaccinated (declined) 790 30 4 (2-5) <5 – 20 67 (50-84) <5 – 10 33 (16-50) <5 –
Vaccination status Un-vaccinated 2310 120 5 (4-6) <5 – 60 50 (41-59) <5 – 60 50 (41-59) <5 –
Vaccination status One vaccination 1580 130 8 (7-10) <5 – 70 54 (45-62) <5 – 50 38 (30-47) <5 –
Vaccination status Two vaccinations 7330 520 7 (7-8) 10 2 (1-3) 280 54 (50-58) <5 – 220 42 (38-47) 10 2 (1-3)
Vaccination status Three or more vaccinations 38720 5660 15 (14-15) 100 2 (1-2) 3190 56 (55-58) <5 – 2340 41 (40-43) 40 1 (0-1)
* All percentages (%) are caluclated with 95% confidence intervals

Concordance with guidance

Of the 6460 patients who received treatment for COVID-19 between 11-Dec-2021 and 23-Feb-2022, 1,255 patients were missing records needed to confirm eligibility. It is likely that most, if not all, of these patients meet all of the eligibility criteria and none of the exclusion criteria but, for example, their SARS-CoV-2 test result was not available in their record or we just do not have access to all the criteria the clinician might use to assess high risk group status (such as the patients identified via non-digital methods).

Figure 4: Breakdown of eligibility criteria variables in treated patients with missing records needed to confirm eligibility

Figure 4: Breakdown of eligibility criteria variables in treated patients with missing records needed to confirm eligibility

Time to treatment

Figure 4a: Time between positive SARS-CoV-2 test and treatment for COVID-19, broken down by treatment type

Figure 4a: Time between positive SARS-CoV-2 test and treatment for COVID-19, broken down by treatment type

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Figure 4b: Time between positive SARS-CoV-2 test and treatment for COVID-19, broken down by high risk cohort

Figure 4b: Time between positive SARS-CoV-2 test and treatment for COVID-19, broken down by high risk cohort

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Brief Methods

Full methods in code form can be found in the accompanying antibody-and-antiviral-deployment repository and are also described in our paper, linked above. Brief methods are given below.

Data sources

All data were analysed securely through OpenSAFELY-TPP https://opensafely.org. Contains the full pseudonymised primary care records for all patients currently registered with general practices using TPP SystmOne software (approximately 23.4 million, 40% of the English population). Data are linked with accident and emergency (A&E) attendance and in-patient records from NHS Digital; national coronavirus testing records from the Second Generation Surveillance System (SGSS); and the “COVID-19 therapeutics dataset”, a patient-level dataset on antiviral and nMAB treatments from NHS England, derived from software used to notify NHS England of COVID-19 treatments.

Study population

Base population: - Patients in OpenSAFELY-TPP registered with a general practice on 11th December 2021 (earliest possible date for eligibility for receiving antivirals/nMABS in outpatient settings).Patients with unknown date of birth excluded.

Eligible patients: - Eligibility and exclusion criteria were applied as per the Interim Clinical Commissioning Policy for non-hospitalised COVID-19 patients (NHSE, 28/01/2022): symptomatic SARS-CoV-2 infection not requiring hospitalisation or supplemental oxygen, in a ‘high risk’ cohort, no known hypersensitivity reaction to relevant active substances). - To determine high risk status we applied the detailed codelists and logic from NHS Digital as far as possible. - We also included patients in the eligible population if they were in the Treated cohort below.

Treated patients: - Treatments and the date they were given were identified in the COVID-19 therapeutics dataset, restricted to those treated in the community (“non_hospitalised”). - Patients issued more than one treatment within two weeks of one another, or with an implausible treatment date (e.g. far in the future) were excluded.

Key demographic and clinical characteristics

We classified patients by age group, sex, NHS region of their general practice and other key demographics including ethnicity (White, Black, Asian or Asian British, Mixed, Other, and Unknown), and Index of Multiple Deprivation (IMD, in quintiles, derived from patient postcode at lower super output area level). Individuals with missing sex, ethnicity, IMD or region were included as “Unknown”. Treated patients were also grouped by whether they had autism, dementia, learning disability, serious mental illness, were resident in a care home or housebound, and by vaccination status.

Concordance with guidance

For patients who received treatment but who were not otherwise identified in the eligible population, we report which eligibility or exclusion criteria were not met (e.g. no positive SARS-CoV-2 test result). Where possible within available data, we also report other potential breaches in guidance for patients receiving treatment, such as not being treated within the prescribed timescale (see Table S2 in the supplementary material for implementation details).

Descriptive statistics

Charts of eligibility and treatment coverage were generated for all high risk cohorts, and stratified by treatment type. Charts showing the weekly proportion of eligible people receiving each treatment were also generated, again stratified by treatment type. Simple descriptive statistics were also used to summarise the counts and proportions of eligible patients treated, stratified by high risk cohort, treatment type and by selected clinical and demographic group. Charts and results not presented in this report are available online for inspection in the associated Github antibody-and-antiviral-deployment repository. Patient counts are rounded to the nearest 10 to protect against small number differences in our routinely updating data.

Codelists

Detailed information on compilation and sources for every individual codelist are available at https://www.opencodelists.org/.